Alpha-fetoprotein changes prior to therapy predict overall survival of patients with hepatocellular carcinomas

Background:

Hepatocellular Carcinoma (HCC) is a leading cause of death in cirrhotic patients and ranks among the most lethal cancers worldwide. Novel biomarkers for early detection and accurate prediction of prognosis are urgently needed to improve patient management. Alpha-fetoprotein (AFP) is a well-established and widely used biomarker for HCC. However, diagnostic accuracy of “static” AFP-values is limited and clinical potential as a prognostic and/or predictive marker needs to be more precisely defined. Therefore, we evaluated the prognostic impact of pre-treatment serum AFP dynamics on the overall survival (OS) of HCC-patients in a German cohort.

Methods:

We retrospectively analyzed patients with confirmed HCC (n = 859) treated at the University Medical Center of the Johannes Gutenberg-University Mainz between 1998 and 2014. Baseline parameters concerning patient status, tumor size and liver function, as well as pre-treatment static and dynamic AFP were investigated. AFP-slope was defined as the delta of two pre-treatment measurements normalized to daily increment/decline. Prognostic impact was assessed using Kaplan-Meier analyses as well as by univariate and multivariate cox regression models. Optimal-cut-off values were defined using receiver operating characteristic curves.

Results:

In univariate cox regression analyses, single AFP-value failed to show a prognostic impact (p = 0.81), while pre-treatment AFP-slope showed a strong association to OS (p = 3.97e-07). Besides several known clinical parameters such as Child Pugh B (p = 0.0006) and C (p = 3.39e-06), portal vein thrombosis (PVT) (p = 2.8e-09), extrahepatic spread (p = 0.0001) and tumor size (p = 1.64e-10), pre-treatment AFP-slope (p = 7.14e-07) could be confirmed as an independent factor on OS of HCC-patients in multivariate analyses. Receiver operating characteristic analysis showed that the best discriminant cut-off value was a pre-treatment AFP-slope greater than 0.0752 ng/ml/day. At this cut-off sensitivity was 53.4% and specificity reached 75.4%. Patients with an AFP-slope greater than 0.0752 ng/ml/day prior to liver transplantation, resection, local ablation or Sorafenib-therapy had a worse overall survival than those with an AFP-slope under the threshold.

Conclusion:

AFP changes prior to therapy are predictive for the overall survival of HCC-patients. The addition of an AFP-slope to established prognostic parameters might improve prognostic classification of HCC.